The present invention relates to non-planar microfluidic devices and methods for their use and manufacture. These devices are useful in various liquid-distribution devices and sensing applications.
There has been a growing interest in the manufacture and use of microfluidic systems for the acquisition of chemical and biological information. In particular, microfluidic systems allow complicated biochemical reactions to be carried out using very small volumes of liquid. These miniaturized systems improve the response time of the reactions, minimize sample volume, and lower reagent cost.
Traditionally, these microfluidic systems have been constructed in a planar fashion using techniques that are borrowed from the silicon fabrication industry. Representative systems are described, for example, in some early work by Manz et al. (Trends in Anal. Chem. (1990) 10(5): 144-149; Advances in Chromatography (1993) 33: 1-66). In these publications, microfluidic devices are constructed by using photolithography to define channels on silicon or glass substrates and etching techniques to remove material from the substrate to form the channels. A cover plate is bonded to the top of this device to provide closure. Miniature pumps and valves can also be constructed to be integral (e.g., within) such devices. Alternatively, separate or off-line pumping mechanisms are contemplated.
More recently, a number of methods have been developed that allow microfluidic devices to be constructed from plastic, silicone or other polymeric materials. In one such method, a negative mold is first constructed, and plastic or silicone is then poured into or over the mold. The mold can be constructed using a silicon wafer (see, e.g., Duffy et al., Analytical Chemistry (1998) 70: 4974-4984; McCormick et.al., Analytical Chemistry (1997) 69: 2626-2630), or by building a traditional injection molding cavity for plastic devices. Some molding facilities have developed techniques to construct extremely small molds. Components constructed using a LIGA technique have been developed at the Karolsruhe Nuclear Research center in Germany (see, e.g., Schomburg et al., Journal of Micromechanical Microengineering (1994) 4: 186-191), and commercialized by MicroParts (Dortmund, Germany). Jenoptik (Jena, Germany) also uses LIGA and a hot-embossing technique. Imprinting methods in PMMA have also been demonstrated (see, Martynova et.al., Analytical Chemistry (1997) 69: 4783-4789) However, these techniques do not lend themselves to rapid prototyping and manufacturing flexibility. Additionally, the foregoing references teach only the preparation of planar microfluidic structures. Moreover, the tool-up costs for both of these techniques are quite high and can be cost-prohibitive.
The microfluidic devices described above are substantially planar. Planar microfluidic devices, however, are not well-suited to certain applications, such as interfacing with ordinary pipes, cylinders, and other bulk fluid conduits not characterized by flat, planar surfaces. For example, it would be desirable to couple a microfluidic device to a syringe, so as to permit a fluid sample to be introduced directly into the device without additional manipulation. Additionally, conventional microfluidic devices are rigid, rendering them ill-suited for applications where flexibility is desirable. As a result, the utility of conventional microfluidic devices is limited.
In one aspect of the present invention, an inexpensive and robust microfluidic device that is substantially non-planar in configuration is provided. In a separate aspect, a microfluidic device that is flexible, in whole or in part, may be contoured to a variety of non-planar substrates or surfaces while maintaining its functionality.
In another aspect of the invention, a non-planar microfluidic device can be comprised of various polymeric materials, combinations of different polymers, and hybrids of polymeric and other materials such as silicon or glass. Metals and metallic films may also be used.
In a separate aspect of the invention, a microfluidic device comprises one or more stencils sandwiched between substrates. Preferably, the mating surfaces of the substrates are complementary so as to enable a seal with the sandwiched stencil to be formed. Preferably, the mating substrates appear planar during manufacture but may be contoured to various non-planar surfaces. The substrates may be stacked or layered to provide complex microfluidic device geometries having various internal channels. The substrate and stencil layers may all be flexible to permit construction of flexible devices.
In another separate aspect of the invention, a microfluidic device is contoured to a vessel (such as a pipe or section of tubing) that has fluid flowing through the pipe or tubing. Fluidic communication between the contents of the vessel and the microfluidic channels is established with a physical interface. Preferably, a flexible microfluidic device having a port physically contacts a pipe or tube having a radial aperture, with the port aligned to the aperture, to permit fluid to be introduced into or sampled by the device through the aligned port/aperture combination. This sampling can be either continuous or metered.
In another separate aspect of the invention, a nonplanar microfluidic device is removably attached to a vessel with a non-permanent adhesive, preferably a self-adhesive tape. In another separate aspect of the invention, a microfluidic device is contoured to connect to a syringe. Fluid may be exchanged between a syringe and a microfluidic device, advantageously by physically contacting the device to the syringe and aligning an aperture in the syringe with an inlet port in the microfluidic device. Such fluid exchange may, for example, permit fluid contents within the syringe to be sampled, either continuously or by metered sampling. Motion of the syringe plunger may be used to drive the fluidic motion within the microfluidic device. In another separate aspect of the invention, a microfluidic device is contoured to connect to other vessel types, such as a vial or container.
In another separate aspect of the invention, a continuously wrapped microfluidic device may be constructed from a single flexible material layer, and then wrapped either around itself or a vessel to form a completed device. In another separate aspect of the invention, a rewindable microfluidic device may be wrapped or unwrapped from around itself or a vessel, and still maintain the integrity of any fluidic sample contained by the device.
In another separate aspect of the invention, a syringe having multiple internal plungers permit fluid to be transferred to an associated chamber, such as a chamber located in an adjacent microfluidic device, to be filled on the draw stroke of the syringe.
In another separate aspect of the invention, a microfluidic device connects to a vessel having a continuously flowing fluid, the device being connected to the vessel both upstream and downstream of a pressure-reducing device located in the vessel.
In another separate aspect of the invention, methods of transferring fluid between a vessel and a microfluidic device are provided.
In a further aspect, any of the foregoing separate aspects may be combined for additional advantage.
Definitions
The term xe2x80x9cchannelxe2x80x9d or xe2x80x9cchamberxe2x80x9d as used herein is to be interpreted in a broad sense. Thus, it is not intended to be restricted to elongated configurations where the transverse or longitudinal dimension greatly exceeds the diameter or cross-sectional dimension. Rather, such terms are meant to comprise cavities or tunnels of any desired shape or configuration through which liquids may be directed. Such a fluid cavity may, for example, comprise a flow-Express through cell where fluid is to be continually passed or, alternatively, a chamber for holding a specified, discrete amount of fluid for a specified amount of time. xe2x80x9cChannelsxe2x80x9d and xe2x80x9cchambersxe2x80x9d may be filled or may contain internal structures comprising valves or equivalent components.
The term xe2x80x9cmicrofluidicxe2x80x9d as used herein is to be understood, without any restriction thereto, to refer to structures or devices through which fluid(s) are capable of being passed or directed, wherein one or more of the dimensions is less than 500 microns. Additionally, such devices can be constructed using any of the materials described herein, as well as combinations of such materials and similar or equivalent materials.
The term xe2x80x9cflexiblexe2x80x9d as used herein means able to endure strain, particularly due to being bent, folded, or stretched, without breaking or suffering permanent injury. xe2x80x9cFlexiblexe2x80x9d as used herein may or may not further include the properties of being resilient or elastic.
The term xe2x80x9csubstantially non-planarxe2x80x9d as used herein refers to the characteristic of not lying or being formed to necessarily lie within a single plane, at least in substantial part. In other words, a non-planar device according to the present invention may be a rigid device that is manufactured so as not to lie within a single plane, or may be a flexible device that appears to be substantially planar during manufacture but can be contoured or adapted to a non-planar surface. A xe2x80x9csubstantially non-planar surfacexe2x80x9d includes a curved surface, such as along the periphery of a cylinder, cone, or sphere, or a compound surface region such as a comer along the intersection of two planar or non-planar surfaces. In preferred embodiments according to the present invention, microfluidic devices are adapted to interface with (e.g., attach to) curved surfaces or compound surface regions, particular vessel surfaces.
The term xe2x80x9cvesselxe2x80x9d as used herein is to be interpreted in a broad sense. It is intended to refer not only to a container for holding a fluid (including liquids and/or gases), but also to a tube or canal (akin to an artery) in which a fluid is contained and conveyed. Examples of vessels to which microfluidic devices of the present invention may be attached include, but are not limited to, pipes, tubes (including flexible tubing), vials, syringes, tanks, bladders, and other containers with cylindrical, spherical, or curved portions.
The phrase xe2x80x9cadaptably attachedxe2x80x9d as used herein refers to an interaction that may be adjusted or tailored to changing circumstances. An adaptable attachment typically involves contouring to a non-planar surface, which contouring may be performed either during or after manufacture of a device. An adaptable attachment may, but does not necessarily, include interaction between flexible or pliable components.